Merkord J, Weber H, Jonas L, Nizze H, Hennighausen G
Institute of Pharmacology and Toxicology, University of Rostock, Germany.
Hum Exp Toxicol. 1998 Mar;17(3):144-50. doi: 10.1177/096032719801700304.
The present study was done to determine the additional influence of daily ethanol intake (15% in drinking water ad libitum) on long-term toxic effects of a single administration of dibutyltin dichloride (DBTC, 8 mg/kg b.w. i.v.) in pancreas and liver of rats. Pathohistological changes in pancreas, bile duct and liver as well as pathobiochemical parameters of pancreatitis (amylase and lipase activity), liver lesions (alkaline phosphatase activity and bilirubin) and fibrosis (hydroxyproline and hyaluronic acid) were measured 1 day and 1 to 24 weeks after DBTC- and DBTC/ethanol administration. DBTC alone induced in rats an acute interstitial pancreatitis as well as acute bile duct and liver lesions in the early experimental phase. Later on, the acute inflammatory processes in pancreas and liver took a chronic course resulting in pancreatic fibrosis and liver cirrhosis. Ethanol increased the toxic effects of DBTC on pancreas and liver during the acute and chronic course. In the acute phase lasting 1 day to 2 weeks, ethanol enhanced the DBTC toxicity on acinar cell and bilio-pancreatic duct epithelium as well as the formation of obstructive ductal plugs by necrotic cell debris. The obstruction and cholestasis in the DBTC/ethanol-group were significantly stronger as in the DBTC-group. The significant increase of hydroxyproline in urine and hyaluronic acid in serum of the DBTC/ethanol treated rats after 12 to 24 weeks was connected with a more severe chronic inflammatory fibrosis in pancreas and liver in comparison to the DBTC-treated group.
本研究旨在确定每日乙醇摄入量（饮用水中含15%乙醇，随意饮用）对大鼠单次静脉注射二丁基二氯化锡（DBTC，8mg/kg体重）后胰腺和肝脏长期毒性作用的额外影响。在注射DBTC和DBTC/乙醇后1天以及1至24周，测量胰腺、胆管和肝脏的病理组织学变化以及胰腺炎的病理生化参数（淀粉酶和脂肪酶活性）、肝脏损伤（碱性磷酸酶活性和胆红素）和纤维化（羟脯氨酸和透明质酸）。单独使用DBTC在大鼠早期实验阶段诱发急性间质性胰腺炎以及急性胆管和肝脏损伤。随后，胰腺和肝脏的急性炎症过程转为慢性病程，导致胰腺纤维化和肝硬化。乙醇在急性和慢性病程中增强了DBTC对胰腺和肝脏的毒性作用。在持续1天至2周的急性期，乙醇增强了DBTC对腺泡细胞和胆胰管上皮的毒性作用，以及坏死细胞碎片形成阻塞性导管栓子的作用。DBTC/乙醇组的梗阻和胆汁淤积比DBTC组明显更严重。与DBTC处理组相比，DBTC/乙醇处理的大鼠在12至24周后尿中羟脯氨酸和血清中透明质酸的显著增加与胰腺和肝脏更严重的慢性炎症纤维化有关。
